The proposed research is an interdisciplinary effort involving collaboration among the Divisions of Nephrology, Endocrinology and Nuclear Medicine. The research proposals are aimed at: 1) the evaluation of the derangements in serum thyroid hormone levels, thyroid hormone metabolism and distribution and the quantitation of specific tissue uptake of T4, T3 and rT3 in patients with renal diseases in the presence and absence of renal failure; and 2) the elucidation of the potential role of malnutrition in altering T4 and T3 metabolism and of parathyroid hormone in inducing the changes in rT3 metabolism in hyperparathyroid states. Studies will be carried out in normal subjects, in healthy euthyroid individuals with altered serum thyroxine binding globulin levels, in patients with acute and chronic renal failure, nephrotic syndrome and normal glomerular filtration rates, patients with primary hyperparathyroidism and those with hypercalcemia and undetectable parathyroid hormone levels. In addition, serum rT3 kinetic studies and direct tissue quantitation of rT3 content will be carried out in normal dogs, parathyroidectomized animals and in acutely and chronically uremic dogs with intact parathyroid glands and in those subjected to parathyroidectomy. The data obtained from serum disappearance and liver and forearm uptake of 131-I labeled T4, T3 and rT3 in the human studies will be subjected to compartmental analysis using the simultation, analysis and modeling program. The serum rT3 kinetic data from the dog studies will be analyzed by both noncompartmental and compartmental methods. It is anticipated that the results of these studies will provide enhanced definition of the specific nature and tissue sites of the alterations in thyroid hormone metabolism as well as elucidating the factors responsible for inducing these changes. These, in turn may shed light on the mechanisms and clinical significance of the disturbances in thyroid hormone metabolism in nonthyroid illnesses and specifically in renal diseases.